Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease - A population-based study.
Adrenoleukodystrophy
CCALD
Care management
Claims
Epidemiology
HSCT
Health cost
Neurodegenerative diseases
Registry
SNDS
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
10 08 2023
10 08 2023
Historique:
received:
03
10
2022
accepted:
23
07
2023
medline:
14
8
2023
pubmed:
11
8
2023
entrez:
10
8
2023
Statut:
epublish
Résumé
X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. Childhood Cerebral ALD (CCALD) is the most severe form with a poor prognosis if not properly treated during the first years of life. Currently, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely available for CCALD treatment. To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. In this context, the French National Health Data System (SNDS) is a particularly indicated database to collect information meeting these needs. A non-interventional, national, real-life, retrospective study was performed using secondary data from the national ALD registry (LEUKOFRANCE) and SNDS. CCALD patients detected between 2009 and 2018 and successfully matched between LEUKOFRANCE and SNDS were included in this study. Index date was defined as the first CCALD event detected during study period. Subgroups of patients with sufficient follow-up (6 months) and history (1 year) available around index date were analyzed to assess CCALD burden and natural history. 52 patients were included into the matched cohort. Median annual incidence of CCALD was estimated at 4 patients. Median age at CCALD diagnosis was 7.0 years. Among patients without allo-HSCT, five-year overall survival was 66.6%, with 93.3% of them presenting at least one CCALD symptom and 62.1% presenting a least one major functional disability (MFD). Among patients with allo-HSCT, five-year overall survival was 94.4%, with only 11.1% of patients presenting CCALD symptoms, and 16.7% of presenting a MFD. Mean annualized costs were almost twice as important among patients without allo-HSCT, with 49,211€, 23,117€, respectively. Costs were almost exclusively represented by hospitalizations. To the best of our knowledge, this is the most up to date study analyzing CCALD epidemiology, clinical and economic burden in France. The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected.
Sections du résumé
BACKGROUND
X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. Childhood Cerebral ALD (CCALD) is the most severe form with a poor prognosis if not properly treated during the first years of life. Currently, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely available for CCALD treatment. To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. In this context, the French National Health Data System (SNDS) is a particularly indicated database to collect information meeting these needs. A non-interventional, national, real-life, retrospective study was performed using secondary data from the national ALD registry (LEUKOFRANCE) and SNDS. CCALD patients detected between 2009 and 2018 and successfully matched between LEUKOFRANCE and SNDS were included in this study. Index date was defined as the first CCALD event detected during study period. Subgroups of patients with sufficient follow-up (6 months) and history (1 year) available around index date were analyzed to assess CCALD burden and natural history.
RESULTS
52 patients were included into the matched cohort. Median annual incidence of CCALD was estimated at 4 patients. Median age at CCALD diagnosis was 7.0 years. Among patients without allo-HSCT, five-year overall survival was 66.6%, with 93.3% of them presenting at least one CCALD symptom and 62.1% presenting a least one major functional disability (MFD). Among patients with allo-HSCT, five-year overall survival was 94.4%, with only 11.1% of patients presenting CCALD symptoms, and 16.7% of presenting a MFD. Mean annualized costs were almost twice as important among patients without allo-HSCT, with 49,211€, 23,117€, respectively. Costs were almost exclusively represented by hospitalizations.
CONCLUSIONS
To the best of our knowledge, this is the most up to date study analyzing CCALD epidemiology, clinical and economic burden in France. The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected.
Identifiants
pubmed: 37563635
doi: 10.1186/s13023-023-02843-x
pii: 10.1186/s13023-023-02843-x
pmc: PMC10416383
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
238Informations de copyright
© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).
Références
Kirk EP, Fletcher JM, Sharp P, Carey B, Poulos A. X-linked adrenoleukodystrophy: the Australasian experience. Am J Med Genet. 1998;76:420–3.
doi: 10.1002/(SICI)1096-8628(19980413)76:5<420::AID-AJMG10>3.0.CO;2-O
pubmed: 9556302
Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49:512–7.
doi: 10.1002/ana.101
pubmed: 11310629
Jardim LB, da Silva ACF, Blank D, Villanueva MM, Renck L, Costa MLB, et al. X-linked adrenoleukodystrophy: clinical course and minimal incidence in South Brazil. Brain Dev. 2010;32:180–90.
doi: 10.1016/j.braindev.2009.02.002
pubmed: 19269120
Regelmann MO, Kamboj MK, Miller BS, Nakamoto JM, Sarafoglou K, Shah S, et al. Adrenoleukodystrophy: Guidance for adrenal surveillance in males identified by newborn screen. J Clin Endocrinol Metab. 2018;103:4324–31.
doi: 10.1210/jc.2018-00920
pubmed: 30289543
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51.
doi: 10.1186/1750-1172-7-51
pubmed: 22889154
pmcid: 3503704
Aubourg P. Adrénoleucodystrophie liée à l’X. Ann Endocrinol. 2007;68:403–11.
doi: 10.1016/j.ando.2007.04.002
Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Clin Pract Neurol. 2007;3:140–51.
doi: 10.1038/ncpneuro0421
pubmed: 17342190
Raymond GV, Aubourg P, Paker A, Escolar M, Fischer A, Blanche S, et al. Survival and functional outcomes in boys with cerebral adrenoleukodystrophy with and without hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:538–48.
doi: 10.1016/j.bbmt.2018.09.036
pubmed: 30292747
Moser HW, Loes DJ, Melhem ER, Raymond GV, Bezman L, Cox CS, et al. X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients. Neuropediatrics. 2000;31:227–39.
doi: 10.1055/s-2000-9236
pubmed: 11204280
Loes DJ, Hite S, Moser H, Stillman AE, Shapiro E, Lockman L, et al. Adrenoleukodystrophy: a scoring method for brain MR observations. AJNR Am J Neuroradiol. 1994;15:1761–6.
pubmed: 7847225
pmcid: 8333737
Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, et al. International Recommendations for the diagnosis and management of patients with adrenoleukodystrophy: a Consensus-Based Approach. Neurology. 2022;99:940–51.
doi: 10.1212/WNL.0000000000201374
pubmed: 36175155
pmcid: 9687408
Parikh SH, Satwani P, Ahn KW, Sahr NA, Fretham C, Abraham AA, et al. Survival Trends in Infants undergoing allogeneic hematopoietic cell transplant. JAMA Pediatr. 2019;173:e190081.
doi: 10.1001/jamapediatrics.2019.0081
pubmed: 30882883
pmcid: 6503511
Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med Massachusetts Medical Society. 2017;377:1630–8.
doi: 10.1056/NEJMoa1700554
République française. Décret n° 2016 – 1871 du 26 décembre 2016 relatif au traitement de données à caractère personnel dénommé « système national des données de santé ». 2016 – 1871 Dec 26, 2016.
Système National des Données de Santé. Qu’est-ce que le SNDS ? | SNDS [Internet]. [cited 2021 Oct 20]. Available from: https://www.snds.gouv.fr/SNDS/Qu-est-ce-que-le-SNDS .
Direction de la Sécurité Sociale. CHIFFRES CLES 2020 ED2019.pdf [Internet]. [cited 2021 Oct 20]. Available from: https://www.securite-sociale.fr/files/live/sites/SSFR/files/medias/DSS/2020/CHIFFRES%20CLES%202020%20ED2019.pdf .
Moulis G, Lapeyre-Mestre M, Palmaro A, Pugnet G, Montastruc J-L, Sailler L. French health insurance databases: what interest for medical research? Rev Médecine Interne. 2015;36:411–7.
doi: 10.1016/j.revmed.2014.11.009
Tuppin P, de Roquefeuil L, Weill A, Ricordeau P, Merlière Y. French national health insurance information system and the permanent beneficiaries sample. Rev Epidemiol Sante Publique. 2010;58:286–90.
doi: 10.1016/j.respe.2010.04.005
pubmed: 20598822
World Health Organization. ICD-10 Version:2019 [Internet]. [cited 2021 Oct 20]. Available from: https://icd.who.int/browse10/2019/en .
Raffray M, Bayat S, Lassalle M, Couchoud C. Linking disease registries and nationwide healthcare administrative databases: the french renal epidemiology and information network (REIN) insight. BMC Nephrol. 2020;21:25.
doi: 10.1186/s12882-020-1692-4
pubmed: 31992233
pmcid: 6988267
Perlbarg J, Allonier C, Boisnault P, Daniel F, Fur P, Szidon P, et al. Faisabilité et intérêt de l’appariement de données individuelles en médecine générale et de données de remboursement appliqué au diabète et à l’hypertension artérielle. Santé Publique. 2014;26:355.
doi: 10.3917/spub.139.0355
pubmed: 25291884
Didier R, Gouysse M, Eltchaninoff H, Le Breton H, Commeau P, Cayla G, et al. Successful linkage of french large-scale national registry populations to national reimbursement data: improved data completeness and minimized loss to follow-up. Arch Cardiovasc Dis. 2020;113:534–41.
doi: 10.1016/j.acvd.2020.04.006
pubmed: 32712203
Caisse Nationale d’Assurance Maladie. CCAM en ligne - CCAM [Internet]. [cited 2021 Jun 2]. Available from: https://www.ameli.fr/accueil-de-la-ccam/index.php .
Caisse Nationale d’Assurance Maladie. Présentation TNB [Internet]. [cited 2021 Oct 20]. Available from: http://www.codage.ext.cnamts.fr/codif/nabm/index_presentation.php?p_site=AMELI .
Caisse Nationale d’Assurance Maladie, Nomenclatures. NGAP et LPP [Internet]. [cited 2021 Sep 22]. Available from: https://www.ameli.fr/infirmier/exercice-liberal/facturation-remuneration/nomenclatures-ngap-lpp/nomenclatures-ngap-lpp .
World Health Organization. WHOCC – ATC/DDD Index [Internet]. [cited 2021 Jun 2]. Available from: https://www.whocc.no/atc_ddd_index/ .
Ministère des Solidarités et de la Santé. Qu’est-ce que le code CIP 13 et le Datamatrix ? [Internet]. [cited 2021 Oct 20]. Available from: https://solidarites-sante.gouv.fr/soins-et-maladies/medicaments/professionnels-de-sante/suppression-de-la-vignette-pharmaceutique-questions-reponses-a-l-attention-des/article/qu-est-ce-que-le-code-cip-13-et-le-datamatrix .
Insee. Institut national de la statistique et des études économiques [Internet]. [cited 2021 Oct 20]. Available from: https://www.insee.fr/fr/accueil .
Turk BR, Theda C, Fatemi A, Moser AB. X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies. Int J Dev Neurosci Off J Int Soc Dev Neurosci. 2020;80:52–72.
doi: 10.1002/jdn.10003
Mallack EJ, Turk BR, Yan H, Price C, Demetres M, Moser AB, et al. MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines. J Inherit Metab Dis. 2021;44:728–39.
doi: 10.1002/jimd.12356
pubmed: 33373467
pmcid: 8113077
Kühl J-S, Kupper J, Baqué H, Ebell W, Gärtner J, Korenke C, et al. Potential risks to stable long-term outcome of allogeneic hematopoietic stem cell transplantation for children with cerebral X-linked adrenoleukodystrophy. JAMA Netw Open. 2018;1:e180769.
doi: 10.1001/jamanetworkopen.2018.0769
pubmed: 30646031
Bessey A, Chilcott JB, Leaviss J, Sutton A. Economic impact of screening for X-linked adrenoleukodystrophy within a newborn blood spot screening programme. Orphanet J Rare Dis. 2018;13:179.
doi: 10.1186/s13023-018-0921-4
pubmed: 30309370
pmcid: 6182830
Herman M, Jura M, Krakowska K, Barg E. X-linked adrenoleukodystrophy diagnosed in three brothers. Pediatr Endocrinol Diabetes Metab. 2019;25:95–8.
doi: 10.5114/pedm.2019.85821
pubmed: 31343142
Cartier N, Aubourg P. Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-Linked adrenoleukodystrophy. Brain Pathol. 2010;20:857–62.
doi: 10.1111/j.1750-3639.2010.00394.x
pubmed: 20626747
pmcid: 8094635
Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101:364–89.
doi: 10.1210/jc.2015-1710
pubmed: 26760044
Kanakis G, Kaltsas G. Adrenal Insufficiency Due to X-Linked Adrenoleukodystrophy. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000 [cited 2021 Sep 23]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK278944/ .
Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118:1971–8.
doi: 10.1182/blood-2011-01-329235
pubmed: 21586746
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, et al. Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood. 2004;104:881–8.
doi: 10.1182/blood-2003-10-3402
pubmed: 15073029
Mahmood et al. Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: a comparison study. Available from: https://pubmed.ncbi.nlm.nih.gov/17618834/ .
Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. Cham: Springer International Publishing; 2019 [cited 2021 Jul 22]. Available from: http://link.springer.com/ https://doi.org/10.1007/978-3-030-02278-5 .